Screening and Functional Analysis of TPO Gene Mutations in Patients With Congenital Hypothyroidism

ABSTRACT Thyroid peroxidase ( TPO ) gene mutations have been reported as the most commonly reported pathogenic variants in congenital hypothyroidism (CH) caused by thyroid hormone (TH) synthesis disorders, the significance of some mutations remains unclear. The study analyzed 54 children diagnosed with CH who underwent whole‐exome sequencing (WES). Functional analysis of the TPO p.K78Q variant, a novel variant of uncertain significance (VUS), revealed that it caused developmental defects in zebrafish and also disrupted thyroid axis gene expression, decreasing tg , dio1 , dio2 , trβ , nis , ttr and increasing tshβ , trα .